Cardiofaciocutaneous Syndrome

What is cardiofaciocutaneous syndrome?

Cardiofaciocutaneous (CFC) syndrome is a genetic disorder that affects many body parts, especially your heart (cardio-), face (facio-), and skin and hair (cutaneous). The condition also causes developmental delays, intellectual disability and growth problems.

The condition is a type of RASopathy. RASopathies are a group of genetic conditions involving the RAS pathway, which is how your body’s cells communicate with each other.

How common is cardiofaciocutaneous syndrome?

Cardiofaciocutaneous syndrome is rare. Some reports estimate that the condition occurs in 1 of every 810,000 births. Only a few 100 cases have been reported in medical literature.

But scientists believe the number is higher. Mild cases may go undiagnosed, and CFC syndrome can be confused with other genetic conditions.

What are the signs and symptoms of CFC disease?

Signs and symptoms of CFC syndrome vary widely. They can range from mild to severe, and they can affect several different body parts.

CFC syndrome usually involves your heart. Most people with the condition are born with a congenital heart defect, which may cause symptoms right away or later in life. Defects may include:

• Abnormal heart valve that affects the flow of blood from your heart to your lungs.
• Heart murmur.
• Hole in your heart between the two lower chambers (ventricular septal defect).
• Hole in your heart between the two upper chambers (atrial septal defect).
• Weak heart muscle (hypertrophic cardiomyopathy).

Almost everyone with this disorder has signs of CFC syndrome that affect their skin and hair, like:

• Dry, rough skin.
• Dark moles (nevi).
• Eyelashes or eyebrows that are sparse or missing.
• Hair that’s sparse, brittle, dry and curly.
• Small bumps on their arms, legs and face (keratosis pilaris).
• Wrinkled palms of their hands and soles of their feet.

The syndrome also involves abnormal facial features.

• Broad, long face.
• Drooping eyelids (ptosis).
• Eyes that are widely spaced and slant downward.
• High forehead with narrow sides.
• Large head (macrocephaly).
• Low-set ears.
• Short nose.
• Small chin.

Children with this condition also may experience:

• Developmental delays and intellectual disability, often moderate to severe.
• Difficulty eating.
• Hydrocephalus (excess fluid in their brain).
• Low levels of growth hormones.
• Seizures.
• Trouble gaining weight and growing (failure to thrive).
• Vision problems.
• Weak, floppy muscles (hypotonia).

What causes cardiofaciocutaneous syndrome?

Cardiofaciocutaneous syndrome is caused by a mutation (change) to one of several genes:

• BRAF gene (most common).
• MAP2K1 and MAP2K2 (second most common).
• KRAS gene (rare).

These genes give your body instructions to make proteins that are important to cell communication. That communication is known as the RAS/MAPK pathway, and it’s essential to fetal development.

Some people who’ve been diagnosed with CFC syndrome don’t have one of the genetic mutations. Scientists believe that those people may have Costello syndrome or Noonan syndrome instead.

Is CFC syndrome inherited?

Most cases of cardiofaciocutaneous syndrome aren’t inherited. The gene mutation usually occurs spontaneously (randomly) during fetal development. Most people with the disorder have no family history of it.

Rarely, the syndrome can be passed down. When it’s inherited, it’s an autosomal dominant condition. That means you only need one copy of the mutated gene from one unaffected parent who carries the mutation.

How is it diagnosed?

Cardiofaciocutaneous syndrome is sometimes discovered before birth, during prenatal ultrasound. Early signs include extra amniotic fluid (liquid surrounding the fetus) or a head and body that are larger than expected.

But most cases are diagnosed during infancy. When your baby has physical signs of the disorder, a healthcare provider may order tests like:

• Electrocardiogram, echocardiogram or cardiac catheterization to assess your baby’s heart function.
• Molecular genetic testing to identify gene mutations, which usually requires a sample of blood or a cheek swab.
• X-ray, CT scan, MRI or ultrasound to identify any abnormal formation of your baby’s heart, brain or other organs.
• Stereoelectroencephalography to examine brain waves and seizure activity.
• Vision tests such as ophthalmoscopy to look inside your baby’s eyes.

How is cardiofaciocutaneous syndrome treated?

There’s no cure for CFC syndrome. Children with the disorder need a team of specialists, often including:

• Cardiologist.
• Dermatologist.
• Endocrinologist.
• Gastroenterologist.
• Geneticist (gene mutations).
• Neurologist.
• Occupational therapist.
• Ophthalmologist.
• Pediatrician.
• Physical therapist.
• Radiologist.
• Speech therapist.

Treatments vary widely depending on individual needs, but they may include:

• Antibiotics to prevent infections, particularly if your child has certain heart conditions.
• Anticonvulsants to control seizures.
• Feeding tube through your child’s nose or into the skin on their stomach to deliver calories and nutrients.
• Glasses, contact lenses or surgery to improve vision.
• High-calorie, nutrient-rich food sources.
• Lotions or ointments to relieve dry skin.
• Medications to help your child’s heart function better or relieve problems with their digestive system.
• Medications to increase growth hormones.
• Shunt in the space around your child’s brain to drain fluid and relieve pressure.
• Surgery to correct heart abnormalities.
• Some children may require cardiac procedures to fix an abnormal pulmonary valve.

How can I prevent cardiofaciocutaneous syndrome?

Because the condition occurs randomly, there’s no way to prevent the mutation that leads to CFC syndrome.

What’s the outlook with cardiofaciocutaneous syndrome?

The life expectancy for people with CFC syndrome depends on the severity of the symptoms. With proper diagnosis and treatment, many people with the condition have a normal lifespan.

What else should I ask my doctor about cardiofaciocutaneous syndrome?

If your child has CFC syndrome, consider asking your healthcare provider the following questions:

• Could this be Costello syndrome or Noonan syndrome instead? Why or why not?
• Was the genetic mutation inherited or spontaneous?
• Does my child have a heart defect?
• Does my child have excess fluid in their brain?
• Will my child have seizures?
• Is the condition affecting my child’s vision?
• Will my child need surgery or medications?
• How can we make sure my child is getting the nutrition they need?
• Are there any signs or symptoms that I should call you about?
• How severe will the intellectual disability be?
• What specialists should we see and how often?
• Are there any support groups that can help us cope with this condition?
• Do you recommend genetic counseling?

What’s the difference between CFC syndrome and Costello syndrome or Noonan syndrome?

The signs and symptoms of CFC syndrome are similar to Costello syndrome and Noonan syndrome. It can be difficult to tell the three genetic conditions apart, especially in infants.

But the three disorders are caused by different genetic mutations. And unlike CFC syndrome, Costello syndrome increases a person’s chances of developing cancer.